Influenza, Fever, And Autism: How Much Should You Worry?

"A child with autism (three years old) pointing to the fish in an aquarium." The photo demonstrates a controlled randomized test by Kasari, Stephanny Freeman and Tanya Paparella to determine whether intensive training in sharing attention (in this case, pointing at fish) and pretend playing can lay the groundwork for the acquisition of language skills and subsequent normal development. (Photo credit: Wikipedia)

It looks like big news: flu or prolonged fever or taking antibiotics linked to autism in large study of 98,000 children. But let’s take a closer look. First, the story, from NBC, which aired a report on Today:

Doctors trying to find some of the causes of autism put another piece into the puzzle on Monday: They found women who had flu while they were pregnant were twice as likely to have a child later diagnosed with autism. Those who had a fever lasting a week or longer — perhaps caused by flu or maybe by something else — were three times as likely to have an autistic child.

The study of 96,000 children in Denmark raises as many questions as it answers.

This story doesn’t link to the study itself–something that science consumers would very much like articles to do–so you can find the abstract here; the article is paywalled.

What the authors did was take self reports from pregnant women during and after pregnancy in two telephone interviews. That’s issue number one: It’s self report, which is a cost-effective way to get information, particularly from a large population, but also is inherently unreliable. There was no clinical confirmation of an influenza infection, and people notoriously think they have the flu when in fact, they have a bad version of the “common cold.” ETA: I also should note that the questions they asked the women never referred specifically to influenza.

The second issue has to do with the many statistical comparisons the authors made using the information they received. The more comparisons researchers make, the greater the chance that something will look significant when it’s really just a chance result. Consider that famous p value cutoff of 0.05. That means that one time in twenty that value turns up, it’s misleading in implying significance. The more comparisons you make, the more likely some difference will look important when it’s not. It’s possible to make certain adjustments to make up for this increasing likelihood, but the authors of the current Danish study did not make these adjustments, arguing that they didn’t need to because it is “exploratory.” ETA: In the end, they performed 106 comparisons and say in their paper that none of their statistically significant findings would have survived these adjustments and remained significant.

I’m not just making up these limitations. The authors themselves mention them. They write in their paper that “misreporting of influenza is likely to be considerable.” They also note in the last sentence of their abstract that “The results may be due to multiple testing; the few positive findings are potential chance findings.”

Results from other groups on the outcomes of fever or influenza infection during pregnancy are mixed. Some studies find no connection between infection during pregnancy and autism while others do. In fact, another Danish study from this same group looking at maternal infections across pregnancy found no association between any maternal infection and an autism diagnosis in the child. They did find a limited increased risk of having an autistic child for pregnant women admitted to the hospital for viral infection during the first trimester or having a bacterial infection in the second trimester.

In another study whose authors did confirm clinical influenza (rather than relying solely on self report), the researchers found no increased risk for having a child with autism for women who’d had influenza during pregnancy. Like the current findings, though, this group did confirm an increased risk for having a child with autism or developmental delay for women who had experienced “fever” during pregnancy. These authors also found that the risk fell to near-normal odds, however, if women took anti-fever medication. In this new Danish study, maternal fever in general, even very high fever, was not linked to an increased autism risk in the child, but a fever lasting seven days or longer was.

Other pathogens are known to affect prenatal brain development, so it’s not novel to think that something as potentially virulent as an influenza virus could. But the information so far is mixed. It may be that a prolonged fever has an effect, but whether that’s the fever or the agent causing the fever is an open question.

There’s one thing that was clinically confirmed in this study that no one seems to have highlighted. In this population of 98,000 children born from 1997 to 2003, 976 were diagnosed with autism. That means 1% of this population, currently ages 8 to 14, has autism, a value very close to those emerging in many studies and to the latest estimates for prevalence among 8-year-olds in the United States.

Finally, if you’re pregnant and worried, you can do three things. First, you can get a flu shot, which is recommended anyway for most pregnant women [PDF]. Second, you can find out more about autism, particularly from autistic adults, and learn that having an autistic child is not inevitably a tragic horrorshow that you need to stress about before you even know you’d have one [*see related comment below]. Third, you can enjoy the math in this quote via WebMD from study author Hjordis Osk Atladottir, who notes that “98% of the women in this study who experienced influenza or fever or took antibiotics during pregnancy did not have children with autism.” In the NBC story, he’s quoted as saying 99% didn’t have a child with autism.

You can count me among the “flu-during pregnancy” population. I spiked a four-day 105 fever because of clinically proven influenza in my first trimester of pregnancy with our second son. But he’s not the son who’s autistic.

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My 12 year old son has autism. I had a bladder infection and took antibiotics at 10 weeks, had a flu-like illness with fever at 15 weeks, and was positive for group B strep and took antibiotics at 38 weeks and had IV antibiotics during L&D. I’ve often wondered about any or all of these things contributing. My son was exclusively breast fed but developed an ear infection at 3 weeks, and was given Amoxicillin. He had definite bowel symptoms from that including blood in his stool. The pediatrician didn’t take that seriously at all. I believe that autism is genetically determined but its development is influenced by environmental factors. It’s tragic in that there’s even more uncertainty about his future than with a typical kid and our biggest concern is who will be there for him when we are gone.

The current study found a very limited increased risk with some specific antibiotics, and as I noted, the authors also stated that when applying adjustments for multiple comparisons, none of the findings were significant. Passing on a group beta strep infection to your child would have been far more dire than taking antibiotics for it. One study has found an association between second-trimester maternal bacterial infections requiring hospitalization and autism, but that’s just one study. Blood in the stool of infants is actually more common than you might think, although incredibly alarming, I know, as our youngest son had that by age 1 month (and I was breastfeeding him). All of our children developed ear infections from infancy, but I know hardly any children who haven’t. They are so common.

I know there are countless uncertainties about the flu vaccine, but following are a number of facts I know, and some questions I have for you and the medical profession in general, from my personal experience:

Facts: 1) My wife experienced a severe reaction to the 2010 flu vaccine. She was in a coma for nearly 4 weeks and required 4 months of intense physical rehab to return to a normal life; 2) during my wife’s illness, I had to constantly remind the neurologists handling her case that the only thing that happened to my wife was that she had gotten the flu vaccine; she had not be bitten by a dog, scratched by a cat, gotten a mosquito bite,etc. 3) To “prove” that my wife was having an immune system reaction to the flu vaccine, they proved that nothing else caused her illness; 4) Several doctors, neurologists and infectious disease doctors were extremely defensive about the flu vaccine, and neither they nor the hospital were in anyway connected with the vaccine my wife received; 5) After nearly 4 weeks, the attending neurologist told me “we have concluded that your wife is experiencing at least one and possibly 2 immune system reactions to the flu vaccine….Simply, her immune system is attacking her brain.” 6) Upon administering plasmapheresis, which gradually diluted the troubling antibodies, my wife’s condition gradually improved. 7) My wife’s illness was reported to VAERS only because I demanded it and was persistent in my demands for nearly 3 weeks. 8) It is known that the flu vaccine causes neurological problems, such as those my wife experienced, and other illnesses, such as Guillain-Barre and its varients, yet those reactions are not revealed on the release form signed by recipients of the vaccine.

Questions: 1) Why would numerous independent doctors deny the temporal relationship between my wife’s illness and the flu vaccine for over 3 weeks? 2)Why were several doctors involved in my wife’s case so defensive about the relationship between the flu vaccine and my wife’s illness? Such defensiveness suggests that the doctors are trying to “hide” something. As the spouse of a critically ill patient, all I wanted was for the doctors to be objective in their treatment of my wife; they were anything but. One infectious disease doctor told me, in response to my questions, that the flu vaccine does “so much good for society and that cases like my wife’s are rare.” That provides an interesting insight into his thinking, but it was certainly not comforting while my wife was laying in a coma, near death. 3)Why would the doctors object to reporting my wife’s reaction to VAERS? This is a CDC sponsored collection area for the reporting of vaccine reactions. Is it not for the common good that all reactions be reported so hopefully the medical community can learn from them? 4) Why aren’t all types of known reactions to the flu vaccine required to be included on the Release form vaccine recipients sign? Is the flu vaccine different from other medications that list every possible know reaction in their advertisements and on their labels?

I don’t expect you to answer the questions I have raised, but my point is this: The facts that a)doctors were defensive about the correlation between the flu vaccine and my wife’s illness, b)they were reluctant to report this to VAERS; and c) that all known reactions to the flu vaccine are not fully disclosed on the release forms, create a lot suspision and raise countless numbers of questions that caused me to not beleive what I was being told. It is that simple. All I wanted was objectivity and candor in identifying the cause of my wife’s illnes so that we could come to a speedy resolution. I feel that much of the frustration people opposed to the flu vaccine, and other vaccines, stems from this same lack of objectivity and candor. Frankly, while I can somewhat understand a lack of candor from the pharmaceutical companies, I think we all expect much more objectivity from the doctors who are treating us.

That’s partially my point – Doctors should not be “expecting” anything, particularly when they have, as they admitted, never seen anything quite like my wife’s illness. They should objectively consider all of the facts and circumstances and determine a course of action accordingly. A predispostion to deny a potential causal relationship by the flu vaccine caused my wife to miss over 3 weeks of her life, and to almost die.

This is true; anyone can file one. That’s part of why VAERS is a good thing, and also why it’s a BAD thing – because until it’s verified, anyone can make any claim (ala a vaccine turned them into the Hulk).

AV’ers love to abuse VAERS to claim correlation and causation, but it doesn’t work like that.